Genetic analysis of HLA-DRA region variation in Taiwanese Parkinson’s disease
Introduction
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by both motor and cognitive disabilities. The etiology of the disease is currently believed to be multi-factorial which includes aging, environmental factors, and genetic susceptibility [1]. To date, PD genome-wide association studies (GWAS) studies in North American, European and Asian populations have been published [2], [3], [4], [5], [6], [7], [8], [9], [10], but only SCNA and MAPT have consistently shown association in the majority of studies. The others were not definitively confirmed. Recently, a GWAS recruiting American patients with European ancestry found a new association between PD and human leukocyte antigen (HLA) region, which was designated PARK18, and the strongest association peak was at rs3129882 [7].
The HLA region located in human chromosome 6 contains many genes that are related with our immune system. Accumulating evidence has suggested the relationship between neuroinflammation and the development of PD [11]. The finding of a recent GWAS with possible association of G allele with PD [7] may further contribute to the pathogenesis and treatment of PD. In this study, we aimed to investigate the polymorphism of rs3129882 in HLA region in Taiwanese PD patients.
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Patient population
Patients diagnosed with PD were recruited from the neurology clinics of Chang-Gung Memorial Hospital. The diagnosis of PD was based on the UK PD Society Brain Bank clinical diagnostic criteria [12]. Unrelated healthy adult volunteers matched for age, gender, ethnic origin, and area of residences were recruited as controls. All subjects gave informed consent for the study under a protocol approved by hospital internal ethics and scientific boards.
Genetic analysis
DNA was extracted from leukocytes by using the
Results
A total of 1070 subjects were included. Five hundred and thirty-eight patients (43.7% females) diagnosed with PD by two neurologists specialized in movement disorders (YR Wu and CM Chen). Only one proband with familial PD in the same family was recruited. The mean age at onset (AAO) of PD symptoms was 61.9 ± 11.5 years (range 19–93) and the mean age of recruitment of 532 controls (50.9% female) was 59.7 ± 12.9 years (range 20–90). The frequencies of rs3129882 genotypes and alleles were similar
Discussion
Several evidences have suggested the role of neuroinflammation in the pathogenesis of PD. The evidences include the finding of HLA-DR-positive microglia in the substantia nigra (SN) of PD patients [13], elevated level of various proinflammatory cytokines in the SN, especially tumor necrosis factor (TNF) and interleukin-1-beta (IL-1β) [14] and the possible protective effect of anti-inflammatory drugs against PD [15]. Recent genetic studies have also found many potential susceptible genes in the
Acknowledgments
This work was supported by grant NSC98-2628-B-182A-001-MY3 from the National Science Council, Executive Yuan and grant CMRPG391181 and CMRPG3A0131 from Chang–Gung Memorial Hospital. We also thank the patients and controls for participating in this study. All authors have no conflict of interest to declare.
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